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  Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy"

Beyer, M., Karbach, J., Mallmann, M. R., Zander, T., Eggle, D., Classen, S., et al. (2009). Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy". Cancer research, 69(10), 4346-54. doi:10.1158/0008-5472.CAN-08-3796.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-6454-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-6455-0
Genre: Journal Article

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Beyer-2009-Cancer vaccine enhan.pdf (Any fulltext), 632KB
 
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 Creators:
Beyer, M., Author
Karbach, J., Author
Mallmann, M. R., Author
Zander, T., Author
Eggle, D., Author
Classen, S., Author
Debey-Pascher, S., Author
Famulok, M.1, Author
Jäger, E., Author
Schultze, J. L., Author
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1External Organizations, ou_persistent22              

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Free keywords: CD8-Positive T-Lymphocytes/*cytology/*immunology Cancer Vaccines/therapeutic use Cell Division/immunology Chemokines, C/genetics Clonal Anergy/*immunology Gene Expression Profiling HLA-A2 Antigen/immunology Humans Immunophenotyping Lymphocyte Culture Test, Mixed Lymphocyte Depletion Neoplasms/*genetics/*immunology Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction
 Abstract: Immune-mediated tumor rejection relies on fully functional T-cell responses and neutralization of an adverse tumor microenvironment. In clinical trials, we detected peptide-specific but non-tumor-reactive and therefore not fully functional CD8(+) T cells post-vaccination against tumor antigens. Understanding the molecular mechanisms behind nontumor reactivity will be a prerequisite to overcome this CD8(+) T-cell deviation. We report that these non-tumor-reactive CD8(+) T cells are characterized by a molecular program associated with hallmarks of "division arrest anergy." Non-tumor-reactive CD8(+) T cells are characterized by coexpression of CD7, CD25, and CD69 as well as elevated levels of lck(p505) and p27(kip1). In vivo quantification revealed high prevalence of non-tumor-reactive CD8(+) T cells with increased levels during cancer vaccination. Furthermore, their presence was associated with a trend toward shorter survival. Dynamics and frequencies of non-target-reactive CD8(+) T cells need to be further addressed in context of therapeutic vaccine development in cancer, chronic infections, and autoimmune diseases.

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 Dates: 2009
 Publication Status: Published in print
 Pages: -
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 Rev. Type: -
 Identifiers: Other: 19435912
DOI: 10.1158/0008-5472.CAN-08-3796
ISSN: 1538-7445 (Electronic)
ISSN: 0008-5472 (Linking)
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Title: Cancer research
  Alternative Title : Cancer Res.
Source Genre: Journal
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Pages: - Volume / Issue: 69 (10) Sequence Number: - Start / End Page: 4346 - 54 Identifier: -